We have established conditions for demonstrating that antilipolytic agents, such as prostaglandins, nicotinic acid, and adenosine, inhibit adenylate cyclase in purified fat cell plasma membranes. The antilipolytics inhibit lipolysis in intact cells. Moreover, as with their physiological effects, antilipolytics act only against low activity states of the enzyme. Thus, by both kinetic and pharmacological criteria, these findings indicate that antilipolytic agents exert their effects by acting directly on the adipocyte adenylate cyclase. Examination of adenylate cyclases from different cells strengthens our previous conclusion that adenosine receptors differ both functionally and pharmacologically. Studies with the turkey erythrocyte adenylate cyclase show that the adenosine receptor, like other hormone receptors, acts by releasing bound inhibitory GDP from the GTP-binding regulatory component of the cyclase system.